Der p2‑A20 DNA vaccine attenuates allergic inflammation in mice with allergic rhinitis

Abstract

Allergic rhinitis (AR) is a common disease that requires more convenient, safe and effective antigen-specific immunotherapies. The present study aimed to investigate the therapeutic effect of intranasal administration of a eukaryotic expression vector co-expressing Der p2 and A20 protein (pVAX1-Der p2-A20) on mice with allergic rhinitis. The pVAX1-Der p2-A20 vaccine was prepared and encapsulated into poly(L-lactide-co-glycolide) (PLGA) nanoparticles. An allergic rhinitis Balb/c mouse model was established through intraperitoneal sensitization with recombinant Der p2 and cholera toxin followed by intranasal challenge with recombinant Der p2. The treatment effect of the DNA vaccine on nasal allergic inflammation was evaluated, and serum IgE, sIgE, IgG and cytokine levels were determined by ELISA. The percentage of CD4+CD25+Foxp3+Tregs in the spleen was detected by flow cytometry. The DNA vaccine co-expressing Der p2 and A20 was successfully constructed and encapsulated into PLGA nanoparticles. Der p2-A20 DNA vaccine intranasal administration markedly ameliorated Der p2-induced nasal allergic inflammation. The serum Der p2-specific IgE, IL-4 and IL-13 expression levels were inhibited, while the Der p2-specific IgG1, IgG2a and IFN-γ expression levels in the serum and splenic CD4+CD25+Foxp3+Treg population were significantly increased after Der p2-A20 DNA vaccine treatment. These results indicated that the Der p2-A20 DNA vaccine alleviates nasal allergic inflammation and promotes splenic Treg population in mice with allergic rhinitis.

Nucleic acid vaccines and CpG oligodeoxynucleotides for allergen immunotherapy

“…A plasmid DNA co-expressing Der p 2 and A20 and encapsulated into Poly(lactic-co-glycolic acid) nanoparticles was recently tested in a Der p 2-induced allergic rhinitis mouse model [29]. Although the present study did not show any data on Der p 2 or A20 expression in airway mucosa following intranasal DNA vaccinations, Der p 2-induced nasal allergic inflammation was ameliorated by the treatment.…”

Current research into A20 mediation of allergic respiratory diseases and its potential usefulness as a therapeutic target

“…Subsequently, A20 plays a role in a negative feedback loop by inhibiting key pro-inflammatory signaling pathways, including those controlling NF-kB signaling (11,22). Hu et al reported that intranasal administration of an over-expression vector which could cause simultaneous overexpression of a dust mite antigen, dermatophagoides pteronyssinus (Der p) 2, along with A20 protein in a mouse AR model, led to significantly enhanced infiltration of mononuclear cells in the nasal mucosa, and attenuated the levels of Der p2−specific IgE, IL−4, and IL−13 in serum (24). CD4 + CD25 + Foxp3 + Treg populations were elevated substantially in both serum and spleen by upregulating A20 in Derp 2-induced AR mouse model (Figure 1B).…”

“…Moreover, novel anti-inflammatory functions of A20 have been identified, including those of inhibiting the activation of mitogen-activated protein kinases (MAPKs), modulating the activation of tumor necrosis factor (TNF) receptors and inflammasomes, and limiting the secretion of pro-inflammatory interleukins ( 22 ), demonstrating its potential role in anti-inflammation. Notably, intranasal administration of A20 has shown promising effects in alleviating allergic inflammation in animal models of allergic respiratory diseases ( 23 , 24 ). Herein, we summarize the current data on the mechanism by which A20 regulates allergic diseases, its effects on allergic airway diseases on the basis of experimental evidence from human genetic studies and experimental evidence in animal models, and its potential as a therapeutic target.…”

Formulations for Allergen Immunotherapy in Human and Veterinary Patients: New Candidates on the Horizon

“…The A20, tumor necrosis factor-induced protein 3 (TNFAIP3), is a ubiquitin-modifying protein playing a defensive role in the pathogenesis of allergic diseases. A DNA vaccine coexpressing Der p 2 and ubiquitin A20 encapsulated into nanoparticles used intranasally in a murine model of allergic rhinitis was able to inhibit allergen-specific IgE, IL-4, IL-10, and IL-17 secretion and to increase IgG1, IgG2a, and IFN-γ ( 86 , 87 ).…”

“…PLGA locally induced a regulatory T cell response via the incorporated mediator substances TGF-beta-1, rapamycin, and IL-2 to prevent a subsequent contact dermatitis reaction ( 113 ). In addition to complexing PLGA-particles with allergens, PLGA were complexed with immune-modulating substances such as CpG-ODN for allergy and asthma prevention ( 114 ) and with Der p 2-A20 DNA in allergic rhinitis ( 87 ) in mouse models. There are no studies in companion animals with PLGA.…”